8-72023917-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_007332.3(TRPA1):c.3052-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000996 in 1,551,724 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00072 (5 hom.)
• Consequence: TRPA1 NM_007332.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.000009181
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.814

Genes affected

TRPA1 (HGNC:497): (transient receptor potential cation channel subfamily A member 1) The structure of the protein encoded by this gene is highly related to both the protein ankyrin and transmembrane proteins. The specific function of this protein has not yet been determined; however, studies indicate the function may involve a role in signal transduction and growth control. [provided by RefSeq, Jul 2008]

MSC-AS1 (HGNC:48724): (MSC antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 8-72023917-G-A is Benign according to our data. Variant chr8-72023917-G-A is described in ClinVar as [Benign]. Clinvar id is 3025034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 540 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPA1	NM_007332.3	c.3052-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000262209.5
MSC-AS1	NR_033652.1	n.1029-28622G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPA1	ENST00000262209.5	c.3052-6C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_007332.3	P1
MSC-AS1	ENST00000518916.5	n.392-28622G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00355 AC: 540 AN: 152062 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000983

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00127 AC: 315 AN: 248706 Hom.: 2 AF XY: 0.00104 AC XY: 140 AN XY: 134450

Gnomad AFR exome AF: 0.0139

Gnomad AMR exome AF: 0.00117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.000233

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.000356

Gnomad OTH exome AF: 0.000330

GnomAD4 exome AF: 0.000719 AC: 1006 AN: 1399544 Hom.: 5 Cov.: 24 AF XY: 0.000619 AC XY: 433 AN XY: 699602

Gnomad4 AFR exome AF: 0.0117

Gnomad4 AMR exome AF: 0.00146

Gnomad4 ASJ exome AF: 0.0000391

Gnomad4 EAS exome AF: 0.000640

Gnomad4 SAS exome AF: 0.000201

Gnomad4 FIN exome AF: 0.0000376

Gnomad4 NFE exome AF: 0.000428

Gnomad4 OTH exome AF: 0.000982

GnomAD4 genome AF: 0.00354 AC: 539 AN: 152180 Hom.: 5 Cov.: 33 AF XY: 0.00351 AC XY: 261 AN XY: 74398

Gnomad4 AFR AF: 0.0120

Gnomad4 AMR AF: 0.000981

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.00239 Hom.: 1

Bravo AF: 0.00418

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

MSC-AS1: BS1, BS2; TRPA1: BS1, BS2 -

TRPA1-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 30, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	14
Dann	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000092
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.41		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.41		Position offset: -44
DS_AL_spliceai		0.24		Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs180680340; hg19: chr8-72936152;